Carotid Intima-media Thickness in Patients with Non-alcoholic Fatty Liver Disease Attending a Tertiary Care Center: A Descriptive Cross-sectional Study

ABSTRACT Introduction: Non-alcoholic fatty liver disease is fatty infiltration of the liver in the absence of other causes of steatosis. It is strongly associated with central adiposity, high body mass index, insulin resistance states, hypertension, hyperlipidemia which are features of metabolic syndrome. The objective of study is to find out the carotid intima-media thickness of non alcoholic fatty liver disease patients attending a tertiary care center. Methods: This was a descriptive cross sectional study conducted at National Academy of Medical Sciences, Bir Hospital from July 2018 to June 2019 among 70 diagnosed cases of non alcoholic fatty liver disease based on ultrasound findings. Data collection was started after receiving ethical approval from Institutional Review Board of the Institute. Convenience sampling method was used. Data were entered using Microsoft Excel. The carotid intima-media thickness of both sides were measured by ultrasound. Statistical Package for Social Sciences version 20 was used for analysis. Results: Out of 70 cases, the mean carotid intima-media thickness was 0.7140±0.1796mm on right and 0.7161±0.1828mm on left side. Among 70 cases 45 (64.3%) were Grade II non alcoholic fatty liver disease and 25 (35.7%) were Grade I. It was 0.5720±0.1275mm and 0.7929±0.1546mm in Grade I and II non alcoholic fatty liver disease cases respectively on right side whereas it was 0.5676±0.1259mm and 0.7987±0.1557mm respectively on left side. Conclusions: This study showed increased carotid intima-media thickness in non alcoholic fatty liver disease cases.


INTRODUCTION
Non-alcoholic fatty liver disease (NAFLD) is fatty infiltration of the liver in the absence of other causes of steatosis, such as alcohol consumption characterized by excessive fat accumulation in liver >5-10% of its weight encompassing a spectrum of increasingly severe clinico-pathological conditions -nonalcoholic fatty liver (NAFL) and nonalcoholic steato-hepatitis (NASH) with or without fibrosis/cirrhosis. [1][2][3] The epidemic proportions of NAFLD prevalence is due to sedentary lifestyle, metabolic syndrome and obesity which is correlated to body mass index (BMI), fat distribution, race, ethnicity and sex with several studies showed the association between hepatic steatosis and carotid atherosclerosis. 2,4,5 The overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ultrasound for the detection of moderate-severe fatty liver were good compared to histology (gold standard) in different studies. 6,7 JNMA I VOL 59 I ISSUE 237 I May 2021 So, in this study, we attempt to find carotid intima-media thickness of non alcoholic fatty liver disease patients in different grades of fatty liver, body mass index, place of residence and ethnicity.

METHODS
This was a hospital based descriptive cross-sectional study carried out at National Academy of Medical Sciences (NAMS), Bir Hospital Kathmandu from July 2018 to June 2019. Data collection was started after obtaining an approval from the Institutional Review Board of NAMS (Reference no. 223 dated on 12th Asadh 2075) and informed written consent was also taken from each patient. Patients between 30 to 60 years of age with ultrasonic findings of hyper-echoic liver with negative history of alcohol abuse, either total abstainers or who consumed <20g of alcohol per day (The diagnosis of NAFLD requires the exclusion of alcohol abuse as the cause of liver disease; a daily intake as low as 20g in females and 30g in males may be sufficient to cause alcohol-induced liver disease in some patients (350ml [12 oz] of beer, 120ml [4 oz] of wine, and 45ml [1.5 oz] of hard liquor each contain 10g of alcohol) 8,9 were labeled as NAFLD with other causes, such as viruses, autoimmune responses, metabolic or hereditary factors, and drugs or toxins were ruled out. Patients with clinical evidence of chronic liver conditions (e.g. known case of liver cirrhosis, viral hepatitis, autoimmune hepatitis, use of hepato-toxic drugs), renal disease, cardiovascular events, recent history of acute illness, age >60 yrs or <30 yrs or alcohol consumption >20g/day were excluded from this study.  Studying the observed mean differences as per BMI showed increased CIMT values in both sides in obese (BMI≥30kg/m 2 ) as compared to normal (BMI<25) and overweight (BMI≥25kg/m 2 and <30kg/m 2 ) cases. Likewise, there were increased CIMT values in overweight as compared to normal BMI cases. These results suggest that CIMT values are increased in high BMI cases (Table 3).

DISCUSSION
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and worldwide with increased prevalence currently affecting approximately 30% of adults and 10% of children in the United States in a study done by Wieckowska, et al. 11 Likewise, in studies done by Browning, et al. 12 Volzke, et al. 13 Targher, et al. 14 Younossi, et al. 15 the prevalence were around 33%, 29.9%, 36.3%, 24.24% respectively in general population has been mentioned. Thus, prevalence based on different studies suggest it is around 1/3 rd among general population which is increasing in recent years. NAFLD represents a wide spectrum of conditions ranging from simple fatty liver which generally follows a benign non-progressive clinical course, to non-alcoholic steatohepatitis (NASH), which is a more serious form of NAFLD that may finally progress to cirrhosis and end-stage liver disease. 1,3,[9][10][11][12] The incidence of cardiovascular disease is higher in NAFLD as compared to those without NAFLD and studies have shown it being as a predictor of cardiovascular disease and independent of conventional risk factors. [16][17][18] Chouhan, et al. 19  Till date, the liver biopsy remains the only reliable way to diagnose NASH and establish the presence of fibrosis. Current noninvasive clinically available tests lack accuracy and reliability. So, in the scenario of rapid increase in the prevalence of NAFLD, the significant research effort in developing novel therapies for NASH patients along with noninvasive, simple, reproducible and reliable biomarkers are greatly needed which will not only help in the diagnosis of NASH, but also be useful for assessment of treatment response and prognosis. So, this should remain a research priority in the NAFLD field to prevent NAFLD related morbidity and mortality.
Our study has some limitations. The sample size was small. Our study was descriptive cross sectional study with no controls enrolled. NAFLD which is one of the important causes of increased CIMT was only studied in our study while other parameters like DM, HTN, obesity, hypercholesterolemia, chronic liver disease, smoking etc. which have profound effect on CIMT were excluded just based on clinical history. The detailed clinical examinations and relevant laboratory investigations were not carried out. The diagnosis of NAFLD was exclusively based on ultrasound findings although liver biopsy is the gold standard to diagnose NAFLD which was not carried out in our study.

CONCLUSIONS
Our study showed an increase in CIMT in NAFLD cases with differences in CIMT measurements in different grades of fatty liver, with BMI values, ethnicity and place of residence. Our study showed increased CIMT values with higher grades of fatty liver, higher values of BMI, in Janajati ethnic groups and cases from Kathmandu valley. There is an increase in CIMT in cases of carotid atherosclerosis. Thus, CIMT measurement in NAFLD patients is one of the valuable indicators for assessing carotid atherosclerosis which is an important risk factor for cardiovascular diseases. So, carotid ultrasound is easily available, a cost effective and non-invasive tool for evaluating CIMT to assess carotid atherosclerosis. Thus, an early intervention can be started if there is an increase in CIMT to minimize the possible complications of atherosclerosis in the form of various cardiovascular diseases or events.